Department of Geriatric Medicine, Concord Hospital, Sydney, Australia.
Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA.
Age Ageing. 2022 Aug 2;51(8). doi: 10.1093/ageing/afac156.
Many common chronic diseases and syndromes are ageing-related. This raises the prospect that therapeutic agents that target the biological changes of ageing will prevent or delay multiple diseases with a single therapy. Gerotherapeutic drugs are those that target pathways involved in ageing, with the aims of reducing the burden of ageing-related diseases and increasing lifespan and healthspan. The approach to discovering gerotherapeutic drugs is similar to that used to discover drugs for diseases. This includes screening for novel compounds that act on receptors or pathways that influence ageing or repurposing of drugs currently available for other indications. A novel approach involves studying populations with exceptional longevity, in order to identify genes variants linked with longer lifespan and could be targeted by drugs. Metformin, rapamycin and precursors of nicotinamide adenine dinucleotide are amongst the frontrunners of gerotherapeutics that are moving into human clinical trials to evaluate their effects on ageing. There are also increasing numbers of potential gerotherapeutic drugs in the pipeline or being studied in animal models. A key hurdle is designing clinical trials that are both feasible and can provide sufficient clinical evidence to support licencing and marketing of gerotherapeutic drugs.
许多常见的慢性疾病和综合征都与衰老有关。这就提出了这样一种前景，即针对衰老生物学变化的治疗药物可能会单一疗法来预防或延缓多种疾病。衰老治疗药物是指针对与衰老有关的途径的药物，目的是减轻与衰老有关的疾病负担，延长寿命和健康寿命。发现衰老治疗药物的方法与发现治疗疾病的药物的方法相似。这包括筛选作用于影响衰老的受体或途径的新型化合物，或者重新利用目前用于其他适应症的药物。一种新方法涉及研究具有特殊长寿的人群，以确定与更长寿命相关的基因变体，并可以通过药物来靶向这些基因变体。二甲双胍、雷帕霉素和烟酰胺腺嘌呤二核苷酸的前体是正在进入人体临床试验以评估它们对衰老影响的衰老治疗药物的领跑者。还有越来越多的潜在衰老治疗药物正在研发中，或正在动物模型中进行研究。一个关键的障碍是设计可行的临床试验，并提供足够的临床证据来支持衰老治疗药物的许可和销售。
